The objective of this project is to elucidata the relationship between molecular composition and topographic arrangements of membrane proteins and lipids with reference to plasma membrane function. Topographic localization of aminophospholipids was assessed by covalent modification with the membrane impermeable reagent trinitrobenzene sulfonic acid (TNBS) using intact cells. In human lymphocytes, a new type of phospholipid asymmetry was observed with respect to fatty acyl composition. This phospholipid molecular species asymmetry evident in phosphatidyl-ethanolamine (PE) with more unsaturated species localized on the plasma membrane interior. When human lymphocytes were treated with interferons, the polyunsaturated PE species migrated to the cell surface. These biphasic changes in membrane composition correlated with biphasic changes in the natural killing capacity of cells treated with interferon. Other membrane functional systems including Mn++ stimulated ATPase and ATP-dependent CA++ binding were also investigated in connection with the toxicologic effects of the bioactive agents such as pyrethroids and Mn++.